Artikel
Intramedullary Mg2Ag nails augment callus formation during fracture healing in mice
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Veröffentlicht: | 10. Oktober 2016 |
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Gliederung
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Objectives: Intramedullary stabilization is frequently used to treat long bone fractures. Implants usually remain unless complications arise. Since implant removal can become very challenging with the risk of further tissue damage, biodegradable materials are emerging as alternative options. Magnesium (Mg)-based biodegradable implants have a controllable degradation rate and good tissue compatibility, which makes them attractive for musculoskeletal research. We therefore asked whether biodegradable Mg-based intramedullary nails improve the healing of long bone fractures in mice.
Methods: To address this question, we developed an intramedullary nail made of a novel biodegradable magnesium-silver-alloy (Mg2Ag, 2.5% Ag). Mg2Ag intramedullary nails of 0.8 mm diameter were introduced into the right femur of 8-week old C57Bl/6 male mice. Fracture healing was investigated using the same model after introducing open femoral midshaft fractures. In vivo degradation, biocompatibility, and effects on fracture repair were determined by radiographs, µCT, and bone histomorphometry. Several organs were collected for histology to unravel any adverse effects of the implant. In addition, the effect of Mg2Ag on osteoblast and osteoclast differentiation was investigated in vitro using mouse primary cells.
Results and Conclusion: Compared to steel nails and no implant controls, Mg2Ag implants degraded over time with remnants being still visible 100 days after implantation. During fracture repair, fractures supported by Mg2Ag nails demonstrated enhanced osteoblast function and subsequent bone formation, while osteoclast activity and bone resorption was decreased, leading to an augmented callus formation. We observed a widening of the femoral shaft under steady state and regenerating conditions, which was at least in part due to an uncoupled bone remodeling. However, mice were overall healthy and no differences in body weight or any histological abnormalities in kidney, liver, muscle, or spleen were found. In vitro analyses confirmed the inhibitory effect of Mg2Ag degradation products on osteoclast differentiation and function with no impair of osteoblast function.
These findings indicate that intramedullary Mg2Ag nails may augment bone formation while reducing bone resorption, leading to a larger callus size. These data suggest that Mg2Ag implants might be promising for intramedullary fixation of long bone fractures, a novel concept that has to be further investigated in future studies.